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DNA damage‐induced replication stress results in PA 200‐proteasome‐mediated degradation of acetylated histones
Author(s) -
Mandemaker Imke K,
Geijer Marit E,
Kik Iris,
Bezstarosti Karel,
Rijkers Erikjan,
Raams Anja,
Janssens Roel C,
Lans Hannes,
Hoeijmakers Jan HJ,
Demmers Jeroen AA,
Vermeulen Wim,
Marteijn Jurgen A
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201745566
Subject(s) - erasmus+ , rotterdam study , library science , medicine , history , computer science , art history , cohort study , the renaissance
Histone acetylation influences protein interactions and chromatin accessibility and plays an important role in the regulation of transcription, replication, and DNA repair. Conversely, DNA damage affects these crucial cellular processes and induces changes in histone acetylation. However, a comprehensive overview of the effects of DNA damage on the histone acetylation landscape is currently lacking. To quantify changes in histone acetylation, we developed an unbiased quantitative mass spectrometry analysis on affinity‐purified acetylated histone peptides, generated by differential parallel proteolysis. We identify a large number of histone acetylation sites and observe an overall reduction of acetylated histone residues in response to DNA damage, indicative of a histone‐wide loss of acetyl modifications. This decrease is mainly caused by DNA damage‐induced replication stress coupled to specific proteasome‐dependent loss of acetylated histones. Strikingly, this degradation of acetylated histones is independent of ubiquitylation but requires the PA 200‐proteasome activator, a complex that specifically targets acetylated histones for degradation. The uncovered replication stress‐induced degradation of acetylated histones represents an important chromatin‐modifying response to cope with replication stress.